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Physical exercise prevents memory impairment in an animal model of hypertension through modulation of CD39 and CD73 activities and A2A receptor expression

Cardoso, Andréia Machadoa,b,c; Manfredi, Leandro Henriquea; Zanini, Danielab; Bagatini, Margarete Dulcea; Gutierres, Jessié Martinsb; Carvalho, Fabianob; Tremblay, Alainc; Belló-Klein, Adrianee; Rubin, Maribel Antonellob; Morsch, Vera Mariab; Sévigny, Jeanc,d; Schetinger, Maria Rosa Chitolinab

doi: 10.1097/HJH.0000000000001845

Background: Central nervous system function has been emerging as an approach to understand hypertension-mediated memory dysfunction, and chronic exercise is able to modulate the purinergic system.

Method: Herein, we investigated the effect of chronic swimming training on the purinergic system in cortex and hippocampus of L-NAME-induced hypertensive rats. Male Wistar rats were divided into four groups: Control, Exercise, L-NAME and Exercise L-NAME. Inhibitory avoidance test was used to assess memory status. NTPDase, CD73 and adenosine deaminase activities and expression, and P2 receptors expression were analyzed. Data were analyzed using two-way ANOVA and Kruskal–Wallis tests, considering P less than 0.05.

Results: Physical exercise reduced the blood pressure and prevented memory impairment induced by L-NAME model of hypertension. L-NAME treatment promoted an increase in NTPDase1, NTPDase3 and CD73 expression and activity in the cortex. A2A expression is increased in hippocampus and cortex in the hypertension group and exercise prevented this overexpression.

Conclusion: These changes suggest that hypertension increases adenosine generation, which acts through A2A receptors, and exercise prevents these effects. These data may indicate a possible mechanism by which exercise may prevent memory impairment induced by L-NAME.

aFederal University of Fronteira Sul, Medical School, Chapecó

bBiochemistry and Molecular Biology Department, CCNE, Federal University of Santa Maria, Brazil

cCentre de recherché du CHU de Québec

dDépartement de microbiologie-infectiologie et d’immunologie, Faculté de Médecine, Université Laval, Québec, QC, Canada

eHealth Basic Sciences Institut, Department of Physiology, Federal University of Rio Grande do Sul, Porto Alegre, Brazil

Correspondence to Andréia Machado Cardoso, Federal University of Fronteira Sul, Medical School, Campus Chapecó, Chapecó, SC CEP 89802-112, Brazil. Tel: +55 49 999611000; e-mail:

Abbreviations: ADA, adenosine deaminase; AMP, adenosine monophosphate; ATP, adenosine triphosphate; BP, blood pressure; L-NAME, N(ω)-nitro-L-arginine methyl ester hydrochloride; NOX, nitric oxide content

Received 16 March, 2018

Revised 5 June, 2018

Accepted 6 June, 2018

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